1. Field of Invention
The field of this invention relates to the production of a vaccine effective against swine dysentery, a disease of swine caused by an anaerobic spirochete, Treponema hyodysenteriae.
2. Information Disclosure Statement
T. hyodysenteriae (also known as Serpula hyodysenteriae, see Stanton, et al., J. Sys. Bacteriol., 41:50-58 (1991) has been recognized as the primary etiological agent of swine dysentery (1). Although pigs infected by T. hyodysenteriae may recover and be resistant to subsequent infection by T. hyodysenteriae, efforts to induce immunity by parenteral administration of killed cells of T. hyodysenteriae have met with limited success and are generally ineffective in field use (2). Killed whole-cell T. hyodysenteriae bacterins have been developed, but often use mineral-oil base adjuvants (3) or have not involved pre-treatment of the T. hyodysenteriae cells to increase their effectiveness as a bacterin.
The use of live avirulent strains of T. hyodysenteriae as a vaccine have also been unsuccessful in protecting affected pigs (4,5). Combinations of killed T. hyodysenteriae bacterins followed by live avirulent T. hyodysenteriae vaccines have also been attempted (6).
Killed whole-cell bacterins based on T. hyodysenteriae cells produced by conventional methods have been produced and used in the field. However, the efficacy of these preparations is typically low with vaccinates reported having 50% of the incidence of swine dysentery as unvaccinated controls (7). Other preparations of killed T. hyodysenteriae cells administered as bacterins have also had limited success, with death and clinical signs of swine dysentery reported in both the vaccinated and unvaccinated animals (8).
A principal reason for the inadequate efficacy of vaccines studied to date may be the interference of other T. hyodysenteriae antigens with more functionally immunogenic antigens. A strongly immunogenic antigen which is not protective may be so much more immunogenic than a protective antigen that most of the host animal's immune response is directed against the nonprotective antigen, to the detriment of the host response to the protective antigen. In other words, nonfunctional antigens (those which do not provide disease resistance) may compete with functional antigens. Other reasons for this may be that the functional antigen is concealed by the nonfunctional antigen (sterically) or that antibody produced to the nonprotective antigen blocks the protective antigen which is thus not processed by the host immune system.
Treponema hyodysenteriae is a helical anaerobic spirochaete. As recently as 1988, researchers declared that "little information is available regarding the physiology, cell biochemistry and nutrition" of this organism (13).
Lipooligosaccharides (LOS) have been extracted with hot phenol-water from the other membranes of T. hyodysenteriae serotypes 1 through 7 (14). These LOSs have been used as an antigenic reagent in an enzyme-linked immunosorbent assay for the detection of antibodies to T. hyodysenteriae antigens (16). This left unresolved the question of whether the LOSs were protective antigens suitable for vaccine use. Moreover, some reports suggested that treponemal lipopolysaccharide was toxic.
No admission is made that any of the references cited herein is prior art. The discussion of the references is based solely on their published content and is not binding on Applicants.